Elisa Espinet

Unifying functional experimental systems with clinical predictive technologies for personalized care in PDAC

Juan Carlos López-Gil, Daniele Campa, Cosmeri Rizzato, Elisa Espinet et autres

Pancreatic ductal adenocarcinoma (PDAC) remains a clinical challenge, projected to become the second leading cause of cancer-related death by 2030. Traditional research has historically relied on established PDAC-derived cell lines to establish 2D in vitro models or in vivo xenografts for drug …

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Fibroblastic aspartoacylase suppresses TGFβ-mediated responses and cancer progression

Ianire Astobiza, Catalina Capó-Serra, Cristina Viera, Javier Rodríguez et autres

Metabolic reprogramming is a hallmark of cancer, and the field has predominantly focused on investigating metabolic alterations in tumour cells. However, the relevance, mechanism and consequences of metabolic adaptations in stromal cells remain understudied. Here, we identify aspartoacylase (ASPA) as a metabolic …

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Regulatory elements in the Sox9 locus license the initiation of pancreatic ductal adenocarcinoma

Marta Ballester, Anita Kurilla, Yifan Dai, Leire Bergara-Muguruza et autres

Cellular plasticity enables tissue regeneration but can be hijacked by oncogenic programs. In the pancreas, Kras acts on tissue-specific enhancers to lock regeneration into a pro-inflammatory state that drives cancer initiation. Enhancer transcription, an early event during cell state transitions, generates long …

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Molecular subtypes in pancreatic cancer: from academic promise to clinical reality

Daniela Mercedes D’Empaire Altimari, Michele Bevere, Elisa Espinet, Yvan Martineau et autres

Pancreatic ductal adenocarcinoma (PDAC) continues to rank among the most lethal malignancies, with five-year survival rates stubbornly below 12%. Over the past decade and a half, transcriptomic analyses have consistently identified molecular subtypes - particularly the classical/progenitor (GATA6-high) and basal-like/squamous (GATA6-low) - …

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Epigenetic dysregulation of IRF9 drives excessive interferon signaling in COPD

Maria Llamazares-Prada, Uwe Schwartz, Darius F. Pease, Stephanie T. Pohl et autres

Altered respiratory barrier integrity and impaired lung regeneration are hallmarks of chronic obstructive pulmonary disease (COPD). To investigate the molecular mechanisms driving the impaired regeneration of alveolar epithelial progenitors in COPD, we generated whole-genome DNA methylation and transcriptome maps of sorted human …

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The ER stress inducer ABTL0812/ibrilatazar potentiates standard chemotherapies and mitigates the immunosuppressive microenvironment in preclinical models of pancreatic cancer

Lorena Usero, Guillermo Yoldi, Claudia Faundez-Vidiella, Nora Diéguez-Martínez et autres

A PGLYRP1-related signaling cascade initiated by cancer stem cells influences subtype identity in pancreatic ductal adenocarcinoma

Juan Carlos López-Gil, Antonio Giráldez-Trujillo, Sonia Alcalá, Germán Vallejo-Palma et autres

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Variability vs. phenotype: Multimodal analysis of Dravet syndrome brain organoids powered by deep learning

Isabel Turpin-Moreno, Adriana Modrego, Andrea Martí-Sarrias, Laura García‐González et autres

gene. Brain organoids (BOs) have emerged as reliable models for neurodevelopmental genetic disorders, reproducing human brain developmental milestones and rising as a promising drug testing tool. Here, we determined the underlying molecular DS pathophysiology affecting neuronal connectivity, revealing an early onset excitatory-inhibitory …

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Author Reply to Peer Reviews of Epigenetic dysregulation of IRF9 drives excessive interferon signalling in COPD

Maria Llamazares Prada, Uwe Schwartz, Darius F. Pease, Stephanie T. Pohl et autres

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Regulatory elements of pancreas development license the initiation of pancreatic ductal adenocarcinoma

Marta Ballester, Anita Kurilla, Yifan Dai, H. Carlo Maurer et autres

Abstract Cellular plasticity and transitional cellular states are crucial for tissue regeneration across multiple organs. In the pancreas, oncogenic Kras hijacks this program, acting on tissue-specific enhancers to prevent the resolution of acinar-to-ductal metaplasia (ADM) and lock regeneration into a pro-inflammatory state …

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Site-specific activation of the proton pump inhibitor rabeprazole by tetrathiolate zinc centres

Teresa Marker, Raphael R. Steimbach, Cecilia Perez-Borrajero, Marcin Luzarowski et autres

Proton pump inhibitors have become top-selling drugs worldwide. Serendipitously discovered as prodrugs that are activated by protonation in acidic environments, proton pump inhibitors inhibit stomach acid secretion by covalently modifying the gastric proton pump. Despite their widespread use, alternative activation mechanisms and …

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Variability vs Phenotype: multimodal analysis of Dravet Syndrome Brain Organoids powered by Deep Learning

Isabel Turpin-Moreno, Adriana Modrego, Andrea Martí-Sarrias, Anna Christina Haeb et autres

ABSTRACT Brain organoids (BO) have risen as a reliable model for neurodelopmental disorders (ND), reproducing human brain development milestones. However, their significant intra- and inter-organoid variability compromises their use in advanced tasks such as drug testing. Overcoming experimental variability is crucial for …

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